A major impediment in the development of chitosan nanoparticles (CTS NPs) as effective drug delivery vesicles is their rapid clearance from blood and endosome entrapment. To overcome these problems, a convenient and...A major impediment in the development of chitosan nanoparticles (CTS NPs) as effective drug delivery vesicles is their rapid clearance from blood and endosome entrapment. To overcome these problems, a convenient and promising template system was developed by decorating poly(methacrylic acid) (PMAA) to the surface of 10-hydroxy camptothecin (HCPT)-loaded CTS NPs (HCPT-CTS/ PMAA NPs). The results show that the presence of negatively charged PMAA significantly elongated the blood circulation time of HCPT-CTS NPs from 12 to 24 h, and reduced the blood clearance (C1) from 30.57 to 6.72 mL/h in vivo. The calculated area under curve (AUC0-24h) and terminal elimination half-life (tl/2) of HCPT-CTS/PMAA NPs were 4.37-fold and 2.48-fold compared with those of HCPT-CTS NPs. Furthermore, the positively charged HCPT-CTS/PMAA NPs triggered by tumor acidic microenvironment (pH 6.5) result in a 453-fold higher cellular uptake than the negatively charged counterparts at pH 7.4. Additionally, HCPT-CTS/PMAA NPs have the ability to escape endosomal entrapment via "proton sponge effect" after incubation with HepG2 cells for 3 h at pH 6.5. Taken together, these findings open up a convenient, low-cost, but effective way to prepare HCPT-CTS/PMAA NPs as a candidate for developing vectors with enhanced long blood circulation and endosomal escape ability in future clinical experiments.展开更多
A novel 4H-SiC trench MOSFET is presented and investigated by simulation in this paper.The device features an integrated Schottky barrier diode and an L-shaped P^+shielding region beneath the gate trench and aside one...A novel 4H-SiC trench MOSFET is presented and investigated by simulation in this paper.The device features an integrated Schottky barrier diode and an L-shaped P^+shielding region beneath the gate trench and aside one wall of the gate trench(S-TMOS).The integrated Schottky barrier diode works as a free-wheeling diode in reverse recovery and reverse conduction,which significantly reduces reverse recovery charge(Q_(rr))and reverse turn-on voltage(VF).The L-shaped P^+region effectively shields the coupling of gate and drain,resulting in a lower gate–drain capacitance(C_(gd))and date–drain charge(Q_(gd)).Compared with that of conventional SiC trench MOSFET(C-TMOS),the V_F and Q_(rr)of S-TMOS has reduced by 44%and 75%,respectively,with almost the same forward output current and reverse breakdown voltage.Moreover,the S-TMOS reduces Q_(gd)and C_(gd)by 32%and 22%,respectively,in comparison with C-TMOS.展开更多
This paper deals with the approach to imposing value-added tax (VAT) on financial transactions. The VAT is a highly harmonized consumption tax within the European Union (EU). VAT operational rules have been set do...This paper deals with the approach to imposing value-added tax (VAT) on financial transactions. The VAT is a highly harmonized consumption tax within the European Union (EU). VAT operational rules have been set down by the relevant directive of the Council of the EU. Under the directive, it is possible to select either exemption or taxation of financial transactions. Only the first option is permitted in the Czech Republic. Pros and cons of both models are described, in particular, the problems with determining the difference between financial transactions and other similar performance that must always be subject to tax. Potential lower VAT revenue or tax base assessment, as appropriate, seems to be crucial in the case of the taxation of financial transactions.展开更多
In recent years, against a background of an environmental problem and resource problem, the introduction of RES (renewable energy source) such as wind power generation and PV (photovoltaic generation), EV (electr...In recent years, against a background of an environmental problem and resource problem, the introduction of RES (renewable energy source) such as wind power generation and PV (photovoltaic generation), EV (electric vehicle), and PHEV (Plug-in hybrid electric vehicle) has been expanding. However, various problems have an ongoing discussion. When the production of electricity by RESs exceeds the power consumption, it is possible to cause a steep variation of point voltage and a deviation from a proper voltage range in a distribution system to which RESs are interconnected. When EVs and PHEVs have spread to the distribution system, a new peak power-demand and a steep voltage drop might occur in the midnight charging time zone in case the electricity charges are low. in this paper, the authors analyze the effects on the distribution system under widespread PVs, EVs, and PHEVs. In addition, the authors propose an improvement plan and analyze about the influence and contribution.展开更多
文摘A major impediment in the development of chitosan nanoparticles (CTS NPs) as effective drug delivery vesicles is their rapid clearance from blood and endosome entrapment. To overcome these problems, a convenient and promising template system was developed by decorating poly(methacrylic acid) (PMAA) to the surface of 10-hydroxy camptothecin (HCPT)-loaded CTS NPs (HCPT-CTS/ PMAA NPs). The results show that the presence of negatively charged PMAA significantly elongated the blood circulation time of HCPT-CTS NPs from 12 to 24 h, and reduced the blood clearance (C1) from 30.57 to 6.72 mL/h in vivo. The calculated area under curve (AUC0-24h) and terminal elimination half-life (tl/2) of HCPT-CTS/PMAA NPs were 4.37-fold and 2.48-fold compared with those of HCPT-CTS NPs. Furthermore, the positively charged HCPT-CTS/PMAA NPs triggered by tumor acidic microenvironment (pH 6.5) result in a 453-fold higher cellular uptake than the negatively charged counterparts at pH 7.4. Additionally, HCPT-CTS/PMAA NPs have the ability to escape endosomal entrapment via "proton sponge effect" after incubation with HepG2 cells for 3 h at pH 6.5. Taken together, these findings open up a convenient, low-cost, but effective way to prepare HCPT-CTS/PMAA NPs as a candidate for developing vectors with enhanced long blood circulation and endosomal escape ability in future clinical experiments.
基金supported by the National Key Research and Development Program of China(No.2016YFB0400502)。
文摘A novel 4H-SiC trench MOSFET is presented and investigated by simulation in this paper.The device features an integrated Schottky barrier diode and an L-shaped P^+shielding region beneath the gate trench and aside one wall of the gate trench(S-TMOS).The integrated Schottky barrier diode works as a free-wheeling diode in reverse recovery and reverse conduction,which significantly reduces reverse recovery charge(Q_(rr))and reverse turn-on voltage(VF).The L-shaped P^+region effectively shields the coupling of gate and drain,resulting in a lower gate–drain capacitance(C_(gd))and date–drain charge(Q_(gd)).Compared with that of conventional SiC trench MOSFET(C-TMOS),the V_F and Q_(rr)of S-TMOS has reduced by 44%and 75%,respectively,with almost the same forward output current and reverse breakdown voltage.Moreover,the S-TMOS reduces Q_(gd)and C_(gd)by 32%and 22%,respectively,in comparison with C-TMOS.
文摘This paper deals with the approach to imposing value-added tax (VAT) on financial transactions. The VAT is a highly harmonized consumption tax within the European Union (EU). VAT operational rules have been set down by the relevant directive of the Council of the EU. Under the directive, it is possible to select either exemption or taxation of financial transactions. Only the first option is permitted in the Czech Republic. Pros and cons of both models are described, in particular, the problems with determining the difference between financial transactions and other similar performance that must always be subject to tax. Potential lower VAT revenue or tax base assessment, as appropriate, seems to be crucial in the case of the taxation of financial transactions.
文摘In recent years, against a background of an environmental problem and resource problem, the introduction of RES (renewable energy source) such as wind power generation and PV (photovoltaic generation), EV (electric vehicle), and PHEV (Plug-in hybrid electric vehicle) has been expanding. However, various problems have an ongoing discussion. When the production of electricity by RESs exceeds the power consumption, it is possible to cause a steep variation of point voltage and a deviation from a proper voltage range in a distribution system to which RESs are interconnected. When EVs and PHEVs have spread to the distribution system, a new peak power-demand and a steep voltage drop might occur in the midnight charging time zone in case the electricity charges are low. in this paper, the authors analyze the effects on the distribution system under widespread PVs, EVs, and PHEVs. In addition, the authors propose an improvement plan and analyze about the influence and contribution.